Research
Scientific research is an important part of our mission to promote public awareness about hereditary hemochromatosis and to provide valuable information to patients and physicians. Patients can access research on the diagnosis and treatment of hemochromatosis. Physicians, scientists or other professionals can access a wealth of in-depth resources in our research section.
Select the Full Text link below to view research published in respected medical journals on hemochromatosis and related conditions. These articles are intended to help you understand the latest research. The information provided is not a substitute for advice from your doctor or other health care provider and the Hemochromatosis Information Society is not responsible for any content contained in or available through these documents.
ACG Clinical Guideline: Hereditary Hemochromatosis
The American Journal of Gastroenterology
114(8):p 1202-1218, August 2019.
DOI: 10.14309/ajg.0000000000000315
Abstract
Hereditary hemochromatosis (HH) is one of the most common genetic disorders among persons of northern European descent. There have been recent advances in the diagnosis, management, and treatment of HH. The availability of molecular diagnostic testing for HH has made possible confirmation of the diagnosis for most patients. Several genotype-phenotype correlation studies have clarified the differences in clinical features between patients with the C282Y homozygous genotypes and other HFE mutation patterns. The increasing use of noninvasive tests such as MRI T2* has made quantification of hepatic iron deposition easier and eliminated the need for liver biopsy in most patients. Serum ferritin of <1,000 ng/mL at diagnosis remains an important diagnostic test to identify patients with a low risk of advanced hepatic fibrosis and should be used routinely as part of the initial diagnostic evaluation. Genetic testing for other types of HH is available but is expensive and generally not useful in most clinical settings. Serum ferritin may be elevated among patients with nonalcoholic fatty liver disease and in those with alcoholic liver disease. These diagnoses are more common than HH among patients with elevated serum ferritin who are not C282Y homozygotes or C282Y/H63D compound heterozygotes. A secondary cause for liver disease should be excluded among patients with suspected iron overload who are not C282Y homozygotes. Phlebotomy remains the mainstay of therapy, but emerging novel therapies such as new chelating agents may have a role for selected patients.
Hemochromatosis Patients as Voluntary Blood Donors
Canadian Journal of Gastroenterology
Volume 18 (2004), Issue 6, Pages 393-396
http://dx.doi.org/10.1155/2004/767529
Abstract
The present study was designed to investigate hemochromatosis patients' suitability as blood donors as well as their perceptions and experience with the current public donation system. Participants were gathered from a list of current hemochromatosis patients (n=120) and members of the Canadian Hemochromatosis Society (n=1000). Of the 1120 surveys mailed out to these groups, 801 surveys were returned completed. The sample respondents had a mean age of 57.44 years (SD=12.73; range 19 to 87 years), and 57% were men. It was found that 20% (160) of the respondents have donated blood since their diagnosis; however, only 12% of the respondents indicated that they use voluntary blood donation as a means of maintaining their iron levels. Forty per cent of the respondents indicated that they had been refused from voluntary donation. Despite the fact that in May 2001 the Canadian Blood Services, in collaboration with the Canadian Hemochromatosis Society, began a promotion campaign to encourage hemochromatosis patients to become voluntary blood donors, the present study found that 15% of the respondents reported having been refused from the voluntary blood donation service due to the diagnosis of hemochromatosis. With respect to quality of life, it was found that individuals who donate blood were generally healthier with respect to physical functioning and bodily pain, however, these findings may indicate that hemochromatosis patients who are healthier are better able to donate at public blood banks, rather than that voluntary blood donation has an effect on the donors' physical functioning over phlebotomy clinic users. These study findings suggest that although there may be other medical factors limiting individuals from donating, hemochromatosis patients are interested in being voluntary blood donors and this potential resource is currently under-used.
Citation
Tara E Power and Paul C Adams, “Hemochromatosis Patients as Voluntary Blood Donors,” Canadian Journal of Gastroenterology, vol. 18, no. 6, pp. 393-396, 2004. doi:10.1155/2004/767529
A Multi-Scale Model of Hepcidin Promoter Regulation Reveals Factors Controlling Systemic Iron Homeostasis
PLoS Computational Biology
Volume 10 (2014), Issue 1, e1003421
https://doi.org/10.1371/journal.pcbi.1003421
Abstract
Systemic iron homeostasis involves a negative feedback circuit in which the expression level of the peptide hormone hepcidin depends on and controls the iron blood levels. Hepcidin expression is regulated by the BMP6/SMAD and IL6/STAT signaling cascades. Deregulation of either pathway causes iron-related diseases such as hemochromatosis or anemia of inflammation. We quantitatively analyzed how BMP6 and IL6 control hepcidin expression. Transcription factor (TF) phosphorylation and reporter gene expression were measured under co-stimulation conditions, and the promoter was perturbed by mutagenesis. Using mathematical modeling, we systematically analyzed potential mechanisms of cooperative and competitive promoter regulation by the transcription factors, and experimentally validated the model predictions. Our results reveal that hepcidin cross-regulation primarily occurs by combinatorial transcription factor binding to the promoter, whereas signaling crosstalk is insignificant. We find that the presence of two BMP-responsive elements enhances the steepness of the promoter response towards the iron-sensing BMP signaling axis, which promotes iron homeostasis in vivo. IL6 co-stimulation reduces the promoter sensitivity towards the BMP signal, because the SMAD and STAT transcription factors compete for recruiting RNA polymerase to the transcription start site. This may explain why inflammatory signals disturb iron homeostasis in anemia of inflammation. Taken together, our results reveal why the iron homeostasis circuit is sensitive to perturbations implicated in disease.
Citation
Casanovas, Guillem, et al. “A Multi-Scale Model of Hepcidin Promoter Regulation Reveals Factors Controlling Systemic Iron Homeostasis.” PLoS Computational Biology, vol. 10, no. 1, Feb. 2014, doi:10.1371/journal.pcbi.1003421.
Autoimmune Conditions in 235 Hemochromatosis Probands with HFE C282Y Homozygosity and Their First-Degree Relatives
Journal of Immunology Research
Volume 2015 (2015), Article ID 453046, 11 pages
http://dx.doi.org/10.1155/2015/453046
Abstract
We performed a retrospective study of autoimmune conditions (ACs) in 235 hemochromatosis probands at diagnosis by analyzing age, sex, ACs, history of first-degree family members with ACs (FH), diabetes, heavy ethanol consumption, elevated serum ALT/AST, nonalcoholic fatty liver disease, viral hepatitis, cirrhosis, iron removed to achieve iron depletion (QFe), and positivity for human leukocyte antigen (HLA) haplotypes A∗01, B∗08; A∗02, B∗44; A∗03, B∗07; A∗03, B∗14; and A∗29, B∗44. There were 138 men (58.7%). Median follow-up was 19.6 y. One or more of 19 ACs were diagnosed in each of 35 probands (14.9%). Prevalences of Hashimoto’s thyroiditis, rheumatoid arthritis, and ankylosing spondylitis were 8.1% (95% CI: [5.1, 12.5]), 1.7% [0.6, 4.6], and 0.0085 [0.0015, 0.0337], respectively. Eighteen probands (7.7%) had a FH. Eight probands with ACs had 9 family members with ACs. In a logistic regression, ACs were less likely in men (odds ratio (OR) 0.3 [0.1, 0.6]) and more likely in probands with a FH (OR 4.1 [1.4, 11.8]). Overall ACs risk was not significantly associated with QFe or HLA haplotypes. Estimated survival of probands with and without ACs did not differ significantly. We conclude that ACs are common in hemochromatosis probands, especially women and probands with a FH.
Citation
James C. Barton and J. Clayborn Barton, “Autoimmune Conditions in 235 Hemochromatosis Probands with HFE C282Y Homozygosity and Their First-Degree Relatives,” Journal of Immunology Research, vol. 2015, Article ID 453046, 11 pages, 2015. doi:10.1155/2015/453046
Hemochromatosis (HFE) gene mutations in Brazilian chronic hemodialysis patients
Brazilian Journal of Medical and Biological Research
Volume 38 (2015), Issue 9, Pages 1321-1324
http://dx.doi.org/10.1590/S0100-879X2005000900005
Abstract
Full Text
Patients with chronic renal insufficiency (CRI) have reduced hemoglobin levels, mostly as a result of decreased kidney production of erythropoietin, but the relation between renal insufficiency and the magnitude of hemoglobin reduction has not been well defined. Hereditary hemochromatosis is an inherited disorder of iron metabolism. The importance of the association of hemochromatosis with treatment for anemia among patients with CRI has not been well described. We analyzed the frequency of the C282Y and H63D mutations in the HFE gene in 201 Brazilian individuals with CRI undergoing hemodialysis. The analysis of the effects of HFE mutations on iron metabolism and anemia with biochemical parameters was possible in 118 patients of this study (hemoglobin, hematocrit, ferritin levels, transferrin saturation, and serum iron). A C282Y heterozygous mutation was found in 7/201 (3.4%) and H63D homozygous and heterozygous mutation were found in 2/201 (1.0%) and 46/201 (22.9%), respectively. The allelic frequencies of the HFE mutations (0.017 for C282Y mutation and 0.124 for H63D mutation) did not differ between patients with CRI and healthy controls. Regarding the biochemical parameters, no differences were observed between HFE heterozygous and mutation-negative patients, although ferritin levels were not higher among patients with the H63D mutation (P = 0.08). From what we observed in our study, C282Y/H63D HFE gene mutations are not related to degrees of anemia or iron stores in CRI patients receiving intravenous iron supplementation (P > 0.10). Nevertheless, the present data suggest that the H63D mutation may have an important function as a modulating factor of iron overload in these patients.
Citation
Perícole, F.V., Alves, M.A.V.R., Saad, S.T.O., & Costa, F.F.. (2005). Hemochromatosis (HFE) gene mutations in Brazilian chronic hemodialysis patients. Brazilian Journal of Medical and Biological Research, 38(9), 1321-1324. https://dx.doi.org/10.1590/S0100-879X2005000900005
A novel immunological assay for hepcidin quantification in human serum
PLoS ONE
Volume 4 (2009), Issue 2, e4581
https://doi.org/10.1371/journal.pone.0004581
Abstract
Hepcidin is a 25-aminoacid cysteine-rich iron regulating peptide. Increased hepcidin concentrations lead to iron sequestration in macrophages, contributing to the pathogenesis of anaemia of chronic disease whereas decreased hepcidin is observed in iron deficiency and primary iron overload diseases such as hereditary hemochromatosis. Hepcidin quantification in human blood or urine may provide further insights for the pathogenesis of disorders of iron homeostasis and might prove a valuable tool for clinicians for the differential diagnosis of anaemia. This study describes a specific and non-operator demanding immunoassay for hepcidin quantification in human sera.
Citation
Koliaraki V, Marinou M, Vassilakopoulos TP, Vavourakis E, Tsochatzis E, et al. (2009) A Novel Immunological Assay for Hepcidin Quantification in Human Serum. PLOS ONE 4(2): e4581. https://doi.org/10.1371/journal.pone.0004581
The role of hepatic transferrin receptor 2 in the regulation of iron homeostasis in the body
Frontiers in Pharmacology
Volume 5 (2014), Article 34, 8 pages
https://doi.org/10.3389/fphar.2014.00034
Abstract
Fine-tuning of body iron is required to prevent diseases such as iron-overload and anemia. The putative iron sensor, transferrin receptor 2 (TfR2), is expressed in the liver and mutations in this protein result in the iron-overload disease Type III hereditary hemochromatosis (HH). With the loss of functional TfR2, the liver produces about 2-fold less of the peptide hormone hepcidin, which is responsible for negatively regulating iron uptake from the diet. This reduction in hepcidin expression leads to the slow accumulation of iron in the liver, heart, joints, and pancreas and subsequent cirrhosis, heart disease, arthritis, and diabetes. TfR2 can bind iron-loaded transferrin (Tf) in the bloodstream, and hepatocytes treated with Tf respond with a 2-fold increase in hepcidin expression through stimulation of the bone morphogenetic protein (BMP)-signaling pathway. Loss of functional TfR2 or its binding partner, the original HH protein, results in a loss of this transferrin-sensitivity. While much is known about the trafficking and regulation of TfR2, the mechanism of its transferrin-sensitivity through the BMP-signaling pathway is still not known.
Citation
Worthen, Christal A., and Caroline A. Enns. “The Role of Hepatic Transferrin Receptor 2 in the Regulation of Iron Homeostasis in the Body.” Frontiers in Pharmacology, vol. 5, June 2014, doi:10.3389/fphar.2014.00034.
Dietary Iron Intake and Serum Ferritin Concentration in 213 Patients Homozygous for the HFEC282Y Hemochromatosis Mutation
Canadian Journal of Gastroenterology
Volume 26 (2012), Issue 6, Pages 345-349
http://dx.doi.org/10.1155/2012/676824
Abstract
BACKGROUND: HFEC282Y homozygotes have an increased risk for developing increased iron stores and related disorders. It is controversial whether dietary iron restrictions should be recommended to such individuals.
OBJECTIVE: To determine whether dietary iron content influences iron stores in HFEC282Y homozygotes as assessed by serum ferritin concentration.
DESIGN: Serum ferritin concentration was measured and a dietary iron questionnaire was completed as part of the evaluation of 213 HFEC282Y homozygotes who were identified through screening of >100,000 primary care patients at five Hemochromatosis and Iron Overload Screening (HEIRS) Study Field Centers in the United States and Canada.
RESULTS: No significant relationships between serum ferritin concentration and dietary heme iron content, dietary nonheme iron content or reports of supplemental iron use were found.
CONCLUSION: These results do not support recommending dietary heme or nonheme iron restrictions for HFEC282Y homozygotes diagnosed through screening in North America.
Citation
Victor R Gordeuk, Laura Lovato, James C Barton, et al., “Dietary Iron Intake and Serum Ferritin Concentration in 213 Patients Homozygous for the HFEC282Y Hemochromatosis Mutation,” Canadian Journal of Gastroenterology, vol. 26, no. 6, pp. 345-349, 2012. doi:10.1155/2012/676824
Effects of highly conserved major histocompatibility complex (MHC) extended haplotypes on iron and low CD8+ T lymphocyte phenotypes in HFE C282Y homozygous hemochromatosis patients from three geographically distant areas.
PLoS ONE
Volume 8 (2013), Issue 11, e79990
https://doi.org/10.1371/journal.pone.0079990
Abstract
Hereditary Hemochromatosis (HH) is a recessively inherited disorder of iron overload occurring commonly in subjects homozygous for the C282Y mutation in HFE gene localized on chromosome 6p21.3 in linkage disequilibrium with the human leukocyte antigen (HLA)-A locus. Although its genetic homogeneity, the phenotypic expression is variable suggesting the presence of modifying factors. One such genetic factor, a SNP microhaplotype named A-A-T, was recently found to be associated with a more severe phenotype and also with low CD8(+)T-lymphocyte numbers. The present study aimed to test whether the predictive value of the A-A-T microhaplotype remained in other population settings. In this study of 304 HH patients from 3 geographically distant populations (Porto, Portugal 65; Alabama, USA 57; Nord-Trøndelag, Norway 182), the extended haplotypes involving A-A-T were studied in 608 chromosomes and the CD8(+) T-lymphocyte numbers were determined in all subjects. Patients from Porto had a more severe phenotype than those from other settings. Patients with A-A-T seemed on average to have greater iron stores (p = 0.021), but significant differences were not confirmed in the 3 separate populations. Low CD8(+) T-lymphocytes were associated with HLA-A*03-A-A-T in Porto and Alabama patients but not in the greater series from Nord-Trøndelag. Although A-A-T may signal a more severe iron phenotype, this study was unable to prove such an association in all population settings, precluding its use as a universal predictive marker of iron overload in HH. Interestingly, the association between A-A-T and CD8(+) T-lymphocytes, which was confirmed in Porto and Alabama patients, was not observed in Nord-Trøndelag patients, showing that common HLA haplotypes like A*01-B*08 or A*03-B*07 segregating with HFE/C282Y in the three populations may carry different messages. These findings further strengthen the relevance of HH as a good disease model to search for novel candidate loci associated with the genetic transmission of CD8(+) T-lymphocyte numbers.
Citation
Costa M, Cruz E, Barton JC, Thorstensen K, Morais S, et al. (2013) Effects of Highly Conserved Major Histocompatibility Complex (MHC) Extended Haplotypes on Iron and Low CD8+ T Lymphocyte Phenotypes in HFE C282Y Homozygous Hemochromatosis Patients from Three Geographically Distant Areas. PLOS ONE 8(11): e79990.https://doi.org/10.1371/journal.pone.0079990
Hereditary hemochromatosis: insights from the Hemochromatosis and Iron Overload Screening (HEIRS) Study.
ASH Education Book
January 1, 2009 vol. 2009 no. 1 195-206
doi: 10.1182/asheducation-2009.1.195
Abstract
Hemochromatosis comprises a group of inherited disorders resulting from mutations of genes involved in regulating iron metabolism. The multicenter, multi-ethnic Hemochromatosis and Iron Overload Screening (HEIRS) Study screened ~100,000 participants in the US and Canada, testing for HFE mutations, serum ferritin and transferrin saturation. As in other studies, HFE C282Y homozygosity was common in Caucasians but rare in other ethnic groups, and there was a marked heterogeneity of disease expression in C282Y homozygotes. Nevertheless, this genotype was often associated with elevations of serum ferritin and transferrin saturation and with iron stores of more than four grams in men but not in women. If liver biopsy was performed, in some cases because of evidence of hepatic dysfunction, fibrosis or cirrhosis was often found. Combined elevations of serum ferritin and transferrin saturation were observed in non-C282Y homozygotes of all ethnic groups, most prominently Asians, but not often with iron stores of more than four grams. Future studies to discover modifier genes that affect phenotypic expression in C282Y hemochromatosis should help identify patients who are at greatest risk of developing iron overload and who may benefit from continued monitoring of iron status to detect progressive iron loading.
Citation
McLaren, Gordon D., and Victor R. Gordeuk. “Hereditary Hemochromatosis: Insights from the Hemochromatosis and Iron Overload Screening (HEIRS) Study.” ASH Education Program Book 2009, no. 1 (January 1, 2009): 195–206. https://doi.org/10.1182/asheducation-2009.1.195.
Iron Overload Is Rare in Patients Homozygous for the H63D Mutation
Canadian Journal of Gastroenterology
Volume 28 (2014), Issue 4, Pages 198-202
http://dx.doi.org/10.1155/2014/468521
Abstract
BACKGROUND: Previous research has suggested that the H63D HFE mutation is associated with elevated iron indexes. However, the true penetrance of this mutation remains unclear.
OBJECTIVE: To assess the proportion of H63D homozygotes with laboratory abnormalities consistent with iron overload.
METHODS: The present study was a retrospective analysis of all individuals referred for HFE genotyping in Newfoundland and Labrador between 1999 and 2009, who were found to be homozygous for the H63D mutation. Using electronic health records, results of ferritin, transferrin saturation, aspartate aminotransferase and alanine aminotransferase testing performed closest to the time of genetic testing were recorded for each patient. Iron overload was classified using previously published definitions from the HealthIron study. SPSS version 17.0 (IBM Corporation, USA) was used for descriptive statistics and to compare means using one-way ANOVA.
RESULTS: Between 1999 and 2009, 170 individuals tested positive for H63D/H63D. At the time of genotyping, 28.8% had an elevated mean (± SD) ferritin level of 501±829 μg/L and 15.9% had an elevated transferrin saturation of 0.45±0.18. At genotyping, 94 individuals had sufficient data available to classify iron overload status. Only three (3.2%) had documented iron overload while the majority (85.1%) had no evidence of iron overload. Sixty individuals had follow-up data available and, of these, only four (6.7%) had documented iron overload, while 45 (75.0%) had no evidence of iron overload. Only one individual had evidence of iron overload-related disease at genotyping and at follow-up.
CONCLUSIONS: H63D homozygosity was associated with an elevated mean ferritin level, but only 6.7% had documented iron overload at follow-up. The penetrance of the H63D mutation appeared to be low.
Citation
Melissa Kelley, Nikhil Joshi, Yagang Xie, and Mark Borgaonkar, “Iron Overload Is Rare in Patients Homozygous for the H63D Mutation,” Canadian Journal of Gastroenterology and Hepatology, vol. 28, no. 4, pp. 198-202, 2014. doi:10.1155/2014/468521
Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features
Molecular Psychiatry
(2016) 21, 1599–1607
https://doi.org/10.1038/mp.2015.192
Abstract
The ‘neurodegeneration with brain iron accumulation’ (NBIA) disease family entails movement or cognitive impairment, often with psychiatric features. To understand how iron loading affects the brain, we studied mice with disruption of two iron regulatory genes, hemochromatosis (Hfe) and transferrin receptor 2 (Tfr2). Inductively coupled plasma atomic emission spectroscopy demonstrated increased iron in the Hfe−/−×Tfr2mut brain (P=0.002, n ≥5/group), primarily localized by Perls’ staining to myelinated structures. Western immunoblotting showed increases of the iron storage protein ferritin light polypeptide and microarray and real-time reverse transcription-PCR revealed decreased transcript levels (Po0.04, n ≥5/group) for five other NBIA genes, phospholipase A2 group VI, fatty acid 2-hydroxylase, ceruloplasmin, chromosome 19 open reading frame 12 and ATPase type 13A2. Apart from the ferroxidase ceruloplasmin, all are involved in myelin homeostasis; 16 other myelin-related genes also showed reduced expression (Po0.05), although gross myelin structure and integrity appear unaffected (P40.05). Overlap (Po0.0001) of differentially expressed genes in Hfe−/−×Tfr2mut brain with human gene co-expression networks suggests iron loading influences expression of NBIA-related and myelin-related genes co-expressed in normal human basal ganglia. There was overlap (Po0.0001) of genes differentially expressed in Hfe−/−×Tfr2mut brain and post-mortem NBIA basal ganglia. Hfe−/−×Tfr2mut mice were hyperactive (Po0.0112) without apparent cognitive impairment by IntelliCage testing (P40.05). These results implicate myelinrelated systems involved in NBIA neuropathogenesis in early responses to iron loading. This may contribute to behavioral symptoms in NBIA and hemochromatosis and is relevant to patients with abnormal iron status and psychiatric disorders involving myelin abnormalities or resistant to conventional treatments.
Citation
Heidari, M, D M Johnstone, B Bassett, R M Graham, A C G Chua, M J House, J F Collingwood, et al. “Brain Iron Accumulation Affects Myelin-Related Molecular Systems Implicated in a Rare Neurogenetic Disease Family with Neuropsychiatric Features.” Molecular Psychiatry 21 (January 5, 2016): 1599.
Auditory neuropathy in a patient with hemochromatosis.
Journal of otology
2016 Dec; Vol. 11 (4), pp. 185-191.
https://doi.org/10.1016/j.joto.2016.10.002
Abstract
Objective
To evaluate the auditory function of an individual with genetically confirmed hemochromatosis.
Methods
A 57 year old male with mildly impaired sound detection thresholds underwent a range of behavioural, electroacoustic and electrophysiologic assessments. These included the recording of otoacoustic emissions and auditory brainstem responses, measurement of monaural temporal resolution and evaluation of binaural speech processing. Findings for this patient were subsequently compared with those of 80 healthy controls with similar audiometric thresholds.
Results
The patient showed the three cardinal features of auditory neuropathy, presenting with evidence of normal cochlear outer hair cell function, disrupted neural activity in the auditory nerve/brainstem and impaired temporal processing. His functional hearing ability (speech perception) was significantly affected and suggested a reduced capacity to use localization cues to segregate signals in the presence of background noise.
Conclusion
We present the first case of an individual with hemochromatosis and auditory neuropathy. The findings for this patient highlight the need for careful evaluation of auditory function in individuals with the disorder.
Citation
Rance G, Chisari D. Auditory neuropathy in a patient with hemochromatosis. Journal of otology. 2016;11(4):185-191. doi:10.1016/j.joto.2016.10.002
Liver Iron Retention Estimated from Utilization of Oral and Intravenous Radioiron in Various Anemias and Hemochromatosis in Humans.
International journal of molecular sciences
2020 Feb 06; Vol. 21 (3).
https://doi.org/10.3390/ijms21031077
Abstract
Patients with hereditary hemochromatosis and non-transfusion-dependent hereditary anemia develop predominantly liver iron-overload. We present a unique method allowing quantification of liver iron retention in humans during first-pass of 59 Fe-labeled iron through the portal system, using standard ferrokinetic techniques measuring red cell iron uptake after oral and intravenous 59 Fe administration. We present data from patients with iron deficiency (ID; N = 47), hereditary hemochromatosis (HH; N = 121) and non-transfusion-dependent hereditary anemia (HA; N = 40). Mean mucosal iron uptake and mucosal iron transfer (±SD) were elevated in patients with HH (59 ± 18%, 80 ± 15% respectively), HA (65 ± 17%, 74 ± 18%) and ID (84 ± 14%, 94 ± 6%) compared to healthy controls (43 ± 19%, 64 ± 18%) ( p < 0.05) resulting in increased iron retention after 14 days compared to healthy controls in all groups ( p < 0.01). The fraction of retained iron utilized for red cell production was 0.37 ± 0.17 in untreated HA, 0.55 ± 0.20 in untreated HH and 0.99 ± 0.22 in ID ( p < 0.01). Interestingly, compared to red blood cell iron utilization after oral iron administration, red blood cell iron utilization was higher after injection of transferrin-bound iron in HA and HH. Liver iron retention was considerably higher in HH and HA compared to ID. We hypothesize that albumin serves as a scavenger of absorbed Fe(II) for delivering albumin-bound Fe(III) to hepatocytes.
Citation
van Vuren AJ, van Wijk R, van Beers EJ, Marx JJM. Liver Iron Retention Estimated from Utilization of Oral and Intravenous Radioiron in Various Anemias and Hemochromatosis in Humans. International journal of molecular sciences. 2020;21(3). doi:10.3390/ijms21031077
Utility of hepatic or total body iron burden in the assessment of advanced hepatic fibrosis in HFE hemochromatosis.
Scientific reports
2019 Dec 27; Vol. 9 (1), pp. 20234.
https://doi.org/10.1038/s41598-019-56732-0
Abstract
Development of advanced hepatic fibrosis in HFE Hemochromatosis (HH) is influenced by hepatic iron concentration (HIC) and age. In patients with HH, it is important to assess the likelihood of cirrhosis and thus the need for confirmatory liver biopsy. Therapeutic phlebotomy also provides an estimate of mobilisable iron stores. We determined whether mobilisable iron stores may predict the presence of advanced fibrosis. Retrospective analysis of 137 male and 65 female HH subjects was undertaken. Biochemical, histological and phlebotomy data were available on all subjects. The mean values of HIC, HIC × [age], mobilisable iron, mobilisable iron × [age] and serum ferritin in the cohort were higher in the group with advanced fibrosis. HIC had an optimum sensitivity and specificity of 73% for the diagnosis of advanced liver fibrosis, with a cut-off HIC level of 200 µmol/g (AUROC 0.83, p < 0.0001). AUROC for HIC was greater in females (0.93) than males (0.79). Mobilisable iron had an optimum sensitivity and specificity both of 83% at a cut-off of 9.6 g for the prediction of advanced fibrosis in all subjects (AUROC 0.92, p < 0.0001). Mobilisable iron stores provide a simple, clinically useful indication of the risk of advanced fibrosis and should routinely be considered.
Citation
Chin J, Powell LW, Ramm LE, Ayonrinde OT, Ramm GA, Olynyk JK. Utility of hepatic or total body iron burden in the assessment of advanced hepatic fibrosis in HFE hemochromatosis. Scientific reports. 2019;9(1):20234. doi:10.1038/s41598-019-56732-0
Sub-acute neonatal hemochromatosis in an infant with hypoplastic left heart syndrome on ventricular assist device awaiting transplantation.
Pediatric transplantation
2019 Nov; Vol. 23 (7), pp. e13567.
https://doi.org/10.1111/petr.13567
Abstract
Single‐ventricle pediatric patients, amongst other children waiting for OHT, are a vulnerable population, especially if candidacy is established before any palliation. NH is a rare disease with poor prognosis in the post‐natal period. We present a case of sub‐acute NH diagnosed in an infant with HLHS who was listed for OHT while bridged with a pulsatile paracorporeal VAD, with an emphasis on the evolution of the condition throughout the patient's clinical course and the ultimate decision for compassionate deactivation of VAD.
Citation
Tadros HJ, Gupta D, Childress M, et al. Sub-acute neonatal hemochromatosis in an infant with hypoplastic left heart syndrome on ventricular assist device awaiting transplantation. Pediatric transplantation. 2019;23(7):e13567. doi:10.1111/petr.13567